Traumatic Injury Activates MAP Kinases in Astrocytes: Mechanisms of Hypothermia and Hyperthermia

Abstract Hyperthermia is common following traumatic brain injury (TBI) and has been associated with poor neurologic outcome, and hypothermia has emerged as a potentially effective therapy for TBI, although its mechanism is still unclear. In this study we investigated the effects of temperature modulations on astrocyte survival following traumatic injury and the involved MAPK pathways. Trauma was produced by scratch injury of a monolayer of confluent astrocytes in culture, followed by incubation at hypothermia (30°C), normothermia (37°C), or hyperthermia (39°C). The activation of MAPK pathways including extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38 MAPK were measured at 0, 15, 30, 60, and 120 min after traumatic injury followed by temperature modulation. Apoptosis of astrocytes was assessed by quantitation of cleaved caspase-3 expression 24 h after injury. Our findings showed that only JNK activation at 15 min after trauma was reduced by hypothermia, and th...